Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17.

ABSTRACT

BACKGROUND: MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival (DFS) for letrozole [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole. PATIENTS AND METHODS: An intent-to-treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out. RESULTS: In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of 2383 placebo patients accepted letrozole. At median follow-up of 64 months (range 16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4% (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and showed superiority for letrozole in both node-positive and -negative patients. Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03, P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI 0.39-0.97, P = 0.033). CONCLUSIONS: Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding.